1. Field of the Invention
This invention relates to apparatus and methods for delivery of neutron beams for medical therapy. More particularly, it concerns a neutron delivery system with a bimodal energy spectrum that can be used for both fast-neutron therapy and for fast-neutron therapy augmented by boron neutron capture therapy.
2. Background Art
Although the prior art for neutron therapy is voluminous, the prior art fails to disclose the bimodal energy spectrum of the present invention. For example, see the following prior art references:
U.S. Pat. No. 5,392,319, Feb. 21, 1995, Accelerator-based neutron irradiation, Eggers Phillip E., Dublin, Ohio.
U.S. Pat. No. 4,666,651, May 19, 1987, High energy neutron generator, Barjon, Robert, Grenoble, France Breyaat, Genevieve, Brignod, France.
U.S. Pat. No. 4,139,777, Feb. 13, 1979, Cyclotron and neutron therapy installation incorporating such a cyclotron, Rautenbach, Willem L., 18 Unie Ave., Stellenbosh, Cape Province, South Africa.
U.S. Pat. No. 4,112,306, Sep. 5, 1978, Neutron irradiation therapy machine, Nunan, Craig S., Los Altos Hills, Calif.
U.S. Pat. No. 3,781,564, Dec. 25, 1973, NEUTRON BEAM COLLIMATORS, Lundberg, Derek Anthony Hatfield, England.
U.S. Pat. No. 3,715,597, Feb. 6, 1973, ROTATABLE NEUTRON THERAPY IRRADIATION APPARATUS, Hoffmann, Ernst-Gunther, Hamburg, Germany, Federal Republic of Meyerhoff, Kaus, Hamburg, Germany, Federal Republic of Offermann, Bernd Peter, Hamburg, Germany, Federal Republic of Barthel, Rolf, Hamburg, Germany, Federal Republic of Germany.
Application of neutrons for radiotherapy of cancer has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick, in 1932. Fast neutron radiotherapy was first used by Robert Stone in the Lawrence Berkeley Laboratory in 1938.
This technology has evolved over the years to the point where it is now a reimbursable modality of choice for inoperable salivary gland tumors, and it is emerging, on the basis of recent research data, as a promising alternate modality for prostate cancer, some lung tumors, and certain other malignancies as well. Neutron capture therapy (NCT), a somewhat different form of neutron-based therapy, was proposed in the mid 1930s and, despite some notable failures in early U.S. trials, has attracted a great deal of renewed research interest lately, due to significant improvements in the relevant technology and radiobiological knowledge.
The basic physical processes involved in fast neutron therapy and neutron capture therapy differ in several respects. In fast neutron therapy, neutrons having relatively high energy (approximately 30-50 MeV) are generated by a suitable neutron source and used directly for irradiation of the treatment volume, just as is done with standard photon (x-ray) therapy. Delivery of fast-neutron therapy for cancer is typically accomplished using accelerator based fast neutron sources that generally involve targeting a proton or deuteron beam onto beryllium. Currently available systems employ various types of cyclotron or liner accelerator technology to deliver the necessary proton beam, which impinges on a suitable target, producing neutrons that are subsequently collimated and delivered to the patient via either a fixed beam delivery system, or by a rotating isocentric structure.
In neutron capture therapy, a neutron capture agent, which in current practice is boron-10 (yielding Boron NCT, or BNCT) is selectively taken into the malignant tissue following the administration of a suitable boronated pharmaceutical, preferably into the bloodstream of the patient. At an appropriate time after boron administration, the treatment volume is exposed to a field of thermal neutrons produced by application of an external neutron beam.
The thermal neutrons interact with the boron-10, which has a very high capture cross section in thermal energy range and which, ideally, is present only in the malignant cells. Each boron-neutron interaction produces an alpha particle and a lithium ion. These highly-energetic charged particles deposit their energy within a geometric volume that is comparable to the size of the malignant cell, leading to a high probability of cell inactivation by direct DNA damage.
Because boron is ideally taken up only in the malignant cells, the NCT process offers the possibility of highly selective destruction of malignant tissue, with cellular-level separating of neighboring normal tissue since the neutron sources used for NCT are, themselves, designed to produce a minimal level of damage of normal tissue.
When BNCT is administered as a primary therapy, an epithermal-neutron beam (neutrons having energies in the range of 1 eV to 10 keV) is used to produce the required thermal neutron flux at depth, since these somewhat higher-energy neutrons will penetrate deeper into the irradiation volume before thermalizing, yet they are still not of sufficient energy to inflict unacceptable damage to intervening normal tissue.
A third form of neutron therapy, which is basically a hybrid that combines the features of fast neutron therapy and NCT is also currently a subject of research interest, and constitutes the field of application where this invention is useful. In this type of radiotherapy, a neutron capture agent is introduced preferentially into the malignant tissue prior to the administration of standard fast neutron therapy.
Because a small fraction of the neutrons in fast neutron therapy will be thermalized in the irradiation volume, it is possible to obtain a small incremental absorbed dose from the neutron capture interactions that result. Improved tumor control relative to fast neutron therapy alone using the augmentation concept is clearly promising based on current radiobiological research. However, until now, no NCT augmentation system has been developed that makes a significant improvement over the unaugmented fast neutron therapy.
Additionally, prior art fast-neutron therapy systems are largely located only at major research centers due to the fact that they are physically complex, bulky and require high-level operating staffs to maintain. In general these systems are not well suited for wide-spread, practical, clinical deployment.